Cardiovascular disease has become the main factor of death and birth defects in the world. There are some therapeutic structures and drugs for curative and palliative therapy of the disease, but to the aim of accessing reliable therapy or to postpone onset of disease, especially for individuals with heritable coronary artery disease in their pedigree Genetic engineering technologies are making advances in the field by identifying oligonucleotides with higher potencies which can be easily targeted against almost any gene, particularly interfering RNA (RNAi). Recently, the focus of RNAi approaches has encompassed the use of synthetic sequences to mimic or silence endogenous microRNAs (miRNAs) that are abruptly dysregulated following cardiovascular diseases. In this review, we summarize the role of miRNAs in heart development and vascular system as two main factors of birth defects and adult morbidity and mortality and miRNAS as new therapeutic agents.